Axon Reflex

Hi-receptors in the adrenal medulla stimulates the release of the two catecholamines noradrenaline and adrenaline as well as enkephalins. In the heart, histamine produces negative inotropic effects via Hr receptor stimulation, but these are normally masked by the positive effects of H2-receptor stimulation on heart rate and force of contraction. Histamine Hi-receptors are widely distributed in human brain and highest densities are found in neocortex, hippocampus, nucleus accumbens, thalamus and posterior hypothalamus where they predominantly excite neuronal activity. Histamine Hrreceptor stimulation can also activate peripheral sensory nerve endings leading to itching and a surrounding vasodilatation ( flare ) due to an axonal reflex and the consequent release of peptide neurotransmitters from collateral nerve endings. 

Axon Reflex Axonal Guidance Axonal Membrane Azole... 

It was generally assumed that it cannot and this became known as Dale s Law. During his studies on antidromic vasodilation he wrote (1935) When we are dealing with two different endings of the same sensory neuron, the one peripheral and concerned with vasodilation and the other at a central synapse, can we suppose that the discovery and identification of a chemical transmitter at axon reflex dilation would furnish a hint as to the nature of the transmission process at a central synapse. The possibility has at least some value as a stimulus to further experiments . 

Dilation of arterioles results in an irregular red flare over an area that is generally wider than that due to the capillary dilation. The flare probably results from an axon reflex in which histamine stimulates autonomic nerve endings, causing release of vasodilatory mediators. 

Intradermal injection of histamine causes a characteristic red spot, edema, and flare response that was first described many years ago. The effect involves three separate cell types smooth muscle in the microcirculation, capillary or venular endothelium, and sensory nerve endings. At the site of injection, a reddening appears owing to dilation of small vessels, followed soon by an edematous wheal at the injection site and a red irregular flare surrounding the wheal. The flare is said to be caused by an axon reflex. A sensation of itching may accompany these effects. 

Bernstein, J.E., Swift, R.M., Soltani, K. (1981). Inhibition of axon reflex vasodilation by topically applied capsaicin. J. Invest. Dermatol. 76 394-5. 

The relative importance of many of the mediators is not precisely defined but they interact to produce mucosal oedema, mucus secretion and damage to the ciliated epithelium. Breaching of the protective epithelial barrier allows hyperreactivity to be maintained by bronchoconstrictor substances or by local axon reflexes through exposed nerve fibres. Wheezing and breathlessness result. The bronchial changes also obstruct access of inhaled drug to the periphery, which is why they can fail to give full relief. 

These observations on sensory nerve endings can probably be extended mechanistically and transposed to other sites (e.g. the airways). In skin it seems certain that a local axon reflex is involved in the triple response described by Lewis, whereby there is flush, flare and wheal manifestation of which denotes neurogenic inflammation. Many of these manifestations can be blocked with bradykinin and tachykinin receptor antagonists, and antihistamines, used in concert. It is now presumed that these basic observations in the skin can be applied to conjunctivae and the airways, and there is every reason to suppose that much the same events are involved in (defensive) reaction to exogenous irritant chemicals. 

Buchan, P. and Adcock, J.J., Capsaicin-induced bronchoconstriction in the guinea pig Contribution of vagal cholinergic reflexes, local axon reflexes and their modulation by BW 443C81, Br. J. Pharmacol, 1 105, 448, 1992. 

This consists of (1) a localized red spot extending for a few millimeters around the site of injection that appears within a few seconds and reaches a maximum in about a minute (2) a brighter red flush, or flare, extending about 1 cm or so beyond the original red spot and developing more slowly and (3) a wheal that is discernible in 1-2 minutes and occupies the same area as the original small red spot at the injection site. The initial red spot results from the direct vasodilating effect of histamine (H -receptor-mediated NO production), the flare is due to histamine-induced stimulation of axon reflexes that cause vasodilation indirectly, and the wheal reflects histamine s capacity to increase capillary permeability (edema formation). 

C-fibres play an important role in airway defensive reflexes. They respond to both mechanical (though with a higher threshold than A5-fibres) and chemical stimuli, including sulphur dioxide, capsaicin and bradykiiun (Lee et al. 2001). In certain species they evoke the peripheral release of neuropeptides such as substance P, neu-rokiiun A and CGRP via an axon reflex which leads to bronchoconstriction and... 

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